A biomimetic collagen/heparin multi-layered porous hydroxyapatite orbital implant for in vivo vascularization studies on the chicken chorioallantoic membrane.

BACKGROUND: The vascularization of an orbital implant is a key issue for reducing complications, such as exposure and infection. METHODS: Here, we developed a facile layer-by-layer assembly approach to modify porous hydroxyapatite (pHA) orbital implants with five collagen (COL)/heparin (HEP) multilayers. RESULTS: SEM characterization showed that the average pore size of the pHA/(COL/HEP)5 scaffold was 316.8 ± 77.1 µm. After being coated with five COL/HEP multilayers, the mechanical strength was improved compared with that of the pHA scaffolds. The in vitro assay displayed that the pHA scaffolds covered with COL/HEP multilayers resulted in a larger number of human umbilical vein endothelial cells after being cultured for 14 days. The macroscopic evaluation and semi-quantitative vascular density analysis of the chicken chorioallantoic membrane assay showed that the pHA/(COL/HEP)5 scaffolds resulted in more intense angiogenesis than the pHA scaffolds. CONCLUSIONS: These studies demonstrate that the biomembrane-mimicking coating of COL/HEP multilayers is a simple and effective strategy to endow combined biological performances of pHA orbital implants and to potentially reduce implant-related complications.

Engineered Hydroxyapatite Nanoadjuvants with Controlled Shape and Aspect Ratios Reveal Their Immunomodulatory Potentials.

Hydroxyapatite (HAP) has been formulated as adjuvants in vaccines for human use. However, the optimal properties required for HAP nanoparticles to elicit adjuvanticity and the underlying immunopotentiation mechanisms have not been fully elucidated. Herein, a library of HAP nanorods and nanospheres was synthesized to explore the effect of the particle shape and aspect ratio on the immune responses in vitro and adjuvanticity in vivo. It was demonstrated that long aspect ratio HAP nanorods induced a higher degree of cell membrane depolarization and subsequent uptake, and the internalized particles elicited cathepsin B release and mitochondrial reactive oxygen species generation, which further led to pro-inflammatory responses. Furthermore, the physicochemical property-dependent immunostimulation capacities were correlated with their humoral responses in a murine hepatitis B surface antigen immunization model, with long aspect ratio HAP nanorods inducing higher antigen-specific antibody productions. Importantly, HAP nanorods significantly up-regulated the IFN-γ secretion and CD107α expression on CD8+ T cells in immunized mice. Further mechanistic studies demonstrated that HAP nanorods with defined properties exerted immunomodulatory effects by enhanced antigen persistence and immune cell recruitments. Our study provides a rational design strategy for engineered nanomaterial-based vaccine adjuvants.